Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry.
The increasing accessibility of genetically engineered receptor systems for the study of drug-receptor interaction has led to a corresponding increase in the testing of new drug entities in recombinant receptor systems. In this article Terry Kenakin illustrates some possible conditions within these recombinant systems where the relative stoichiometry of the receptors to other cellular components may differ from that found in natural systems and where this difference may lead to anomalies in drug testing.
Kenakin
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Department of Receptor Biochemistry, Glaxo Wellcome Research and Development, Triangle Park, NC 27709, USA.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005818:Genetic Engineering; D006801:Humans; D008962:Models, Theoretical; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000819:agonists* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
C097350:GPR12 protein, human; C486281:GPR68 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D019204:GTP-Binding Proteins